title: The serine protease marapsin is expressed in stratified squamous epithelia and is up-regulated in the hyperproliferative epidermis of psoriasis and regenerating wounds.
abstract: The trypsin-like serine protease marapsin is a member of the large protease gene cluster at human chromosome 16p13.3, which also contains the structurally related proteases testisin, tryptase epsilon, tryptase gamma, and EOS. To gain insight into the biological functions of marapsin, we undertook a detailed gene expression analysis. It showed that marapsin expression was restricted to tissues containing stratified squamous epithelia and was absent or only weakly expressed in all other tissues, including the pancreas. Marapsin was constitutively expressed in nonkeratinizing stratified squamous epithelia of human esophagus, tonsil, cervix, larynx, and cornea. In the keratinizing stratified squamous epidermis of skin, however, its expression was induced only during epidermal hyperproliferation, such as in psoriasis and in murine wound healing. In fact, marapsin was the second most strongly up-regulated protease in psoriatic lesions, where expression was localized to the upper region of the hyperplastic epidermis. Similarly, in the hyperproliferative epithelium of regenerating murine skin wounds, marapsin localized to the suprabasal layers, where keratinocytes undergo squamous differentiation. The transient up-regulation of marapsin, which closely correlated with re-epithelialization, was virtually absent in a genetic mouse model of delayed wound closure. These results suggested a function during the process of re-epithelialization. Furthermore, in reconstituted human epidermis, a model system of epidermal differentiation, members of the IL-20 subfamily of cytokines, such as IL-22, induced marapsin expression. Consistent with a physiologic role in marapsin regulation, IL-22 was also strongly expressed in re-epithelializing skin wounds. Marapsin's restricted expression, localization, and cytokine-inducible expression suggest a role in the terminal differentiation of keratinocytes in hyperproliferating squamous epithelia.
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Dimitry M
authors.initials: DM
authors.lastname: Danilenko
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Stuart
authors.initials: S
authors.lastname: Bunting
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Ganesan
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Susan
authors.initials: S
authors.lastname: Sa
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Ronald
authors.initials: R
authors.lastname: Ferrando
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Wu
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Ganesh A
authors.initials: GA
authors.lastname: Kolumam
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Departments of Protein Engineering, Pathology, Tumor Biology and Angiogenesis, Bioinformatics, and Immunology, Genentech, Inc., South San Francisco, California 94080. Electronic address: dak@gene.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kirchhofer
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D004817:Epidermis / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology / Q000473:pathology; D051379:Mice; D009928:Organ Specificity; D011565:Psoriasis / Q000201:enzymology* / Q000473:pathology; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D015854:Up-Regulation; D014945:Wound Healing; D014950:Wounds, Penetrating / Q000201:enzymology / Q000473:pathology; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D012697:Serine Endopeptidases; D000097043:Interleukin-22; C472564:PRSS27 protein, human